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“The findings suggest that health care clinicians should carefully evaluate the risk-benefit ratio of benzodiazepines for the treatment of insomnia and mood or anxiety disorders in early pregnancy,” wrote Odile Sheehy, M.Sc., of the Centre Hospitalier Universitaire Sainte-Justine in Montreal and colleagues. “[I]f benzodiazepines are needed, they should be prescribed for short durations.”
Sheehy and colleagues analyzed data from the Quebec Pregnancy Cohort, which included all pregnancies of women aged 15 to 45 who were covered by the Quebec Public Prescription Drug Insurance Plan from January 1, 1998, to December 31, 2015. The researchers excluded data on pregnancies among several groups of women from the analysis, including women exposed to known teratogens during the first trimester, as well as those with a history of epilepsy, previous use of benzodiazepines, and/or planned abortions.
Of the 442,066 pregnancies included in the cohort, 27,149 (6.1%) ended with miscarriage. A pregnant woman was considered to have been exposed to a benzodiazepine if she had filled at least one prescription for any type of benzodiazepine between the first day of the last menstrual period and the date of miscarriage.
Among pregnancies ending with miscarriage, 375 (1.4%) were among women exposed to benzodiazepines in early pregnancy compared with 788 (0.6%) of the 134,305 matched-control pregnancies. After adjusting for potential confounders, including diagnoses of mood and anxiety disorders and insomnia before pregnancy, the researchers found benzodiazepine exposure in early pregnancy was independently associated with an increased risk of miscarriage (adjusted odds ratio, 1.85).
“The risk of [miscarriage] increased with increasing daily dose of benzodiazepines, which may suggest a dose-response effect,” the authors wrote.
Additional analysis revealed that the risk of miscarriage was similar among pregnant women exposed to short-acting benzodiazepines (defined as a half-life less than or equal to 24 hours), such as lorazepam, and long-acting benzodiazepines (defined as a half-life greater than 24 hours), such as diazepam.
The authors noted several limitations of the study, including smaller sample sizes in subgroup analyses on specific benzodiazepine agents, which resulted in lower statistical power, and missing information about smoking and/or alcohol intake behaviors during pregnancy.
For related information, see the Psychiatric News article “Benzodiazepine Use and Misuse Among Adults in the United States.”
(Image: iStock/serezniy)
